Silva Francine R F, Heredia Joyce E, Arntz Onno J, Barrioni Breno R, Teixeira Mauro M, Silva Tarcília A, van de Loo Fons A J, Macari Soraia, Ferreira Adaliene V M, Oliveira Marina C
Immunometabolism, Department of Nutrition, Nursing School, Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, Brazil.
Experimental Rheumatology, Radboud University Medical Center, Nijmegen, the Netherlands.
Mol Nutr Food Res. 2025 Jul 2:e70139. doi: 10.1002/mnfr.70139.
Obesity may cause bone loss due to changes in energy and bone metabolism. Bone loss treatment is still limited, requiring new therapeutic strategies. Bovine milk extracellular vesicles (MEVs) are nanoparticles that act as modulators of cell signaling. While its benefits have already been demonstrated in bone loss, the underlying mechanisms must be better elucidated. To evaluate the effect of MEVs on bone loss in obesity, BALB/c mice were fed a chow diet or a high-refined carbohydrate (HC) diet for 12 weeks and treated or not with MEVs from the 9th week. Mice fed the HC diet showed bone loss in the maxillary and long bones related to detrimental changes in the bone cell profile. As expected, the HC diet induced hyperglycemia and dyslipidemia, lipid accumulation in adipose and liver, and elevated receptor activator of nuclear factor kappa-Β ligand (RANKL)/osteoprotegerin (OPG) ratio and Pentraxin 3 (PTX3) levels. MEV treatment protected from bone loss, increasing osteoblast and osteocyte numbers and reducing osteoclastic activity. Additionally, MEVs diminished adiposity, liver damage, serum glucose, triglyceride, and PTX3 levels, and the RANKL/OPG ratio. MEVs offer a protective effect against bone loss and improve metabolic outcomes in an HC diet-induced obesity model, suggesting that metabolic improvements may contribute to their bone-protective role.
肥胖可能由于能量和骨代谢的变化而导致骨质流失。骨质流失的治疗方法仍然有限，需要新的治疗策略。牛乳细胞外囊泡（MEVs）是作为细胞信号调节剂的纳米颗粒。虽然其在骨质流失方面的益处已经得到证实，但其潜在机制仍需进一步阐明。为了评估MEVs对肥胖引起的骨质流失的影响，将BALB/c小鼠喂食普通饮食或高精制碳水化合物（HC）饮食12周，并从第9周开始用或不用MEVs进行治疗。喂食HC饮食的小鼠在上颌骨和长骨中出现骨质流失，这与骨细胞特征的有害变化有关。正如预期的那样，HC饮食诱导了高血糖和血脂异常、脂肪和肝脏中的脂质积累，以及核因子κB受体激活剂配体（RANKL）/骨保护素（OPG）比值和五聚体3（PTX3）水平升高。MEV治疗可防止骨质流失，增加成骨细胞和骨细胞数量，并降低破骨细胞活性。此外，MEVs减少了肥胖、肝脏损伤、血糖、甘油三酯和PTX3水平以及RANKL/OPG比值。在HC饮食诱导的肥胖模型中，MEVs对骨质流失具有保护作用，并改善代谢结果，这表明代谢改善可能有助于其骨质保护作用。
